Source:http://linkedlifedata.com/resource/pubmed/id/17121861
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2007-2-5
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pubmed:abstractText |
The Artemis nuclease is required for V(D)J recombination and for repair of an as yet undefined subset of radiation-induced DNA double strand breaks. To assess the possibility that Artemis acts on oxidatively modified double strand break termini, its activity toward model DNA substrates, bearing either 3'-hydroxyl or 3'-phosphoglycolate moieties, was examined. A 3'-phosphoglycolate had little effect on Artemis-mediated trimming of long 3' overhangs (> or =9 nucleotides), which were efficiently trimmed to 4-5 nucleotides. However, 3'-phosphoglycolates on overhangs of 4-5 bases promoted Artemis-mediated removal of a single 3'-terminal nucleotide, while at least 2 nucleotides were trimmed from identical hydroxyl-terminated substrates. Artemis also efficiently removed a single nucleotide from a phosphoglycolate-terminated 3-base 3' overhang, while leaving an analogous hydroxyl-terminated overhang largely intact. Such removal was completely dependent on DNA-dependent protein kinase and ATP and was largely dependent on Ku, which markedly stimulated Artemis activity toward all 3' overhangs. Together, these data suggest that efficient Artemis-mediated cleavage of 3' overhangs requires a minimum of 2 nucleotides, or a nucleotide plus a phosphoglycolate, 3' to the cleavage site, as well as 2 unpaired nucleotides 5' to the cleavage site. Shorter 3'-phosphoglycolate-terminated overhangs and blunt ends were also processed by Artemis but much more slowly. Consistent with a role for Artemis in repair of terminally blocked double strand breaks in vivo, human cells lacking Artemis exhibited hypersensitivity to x-rays, bleomycin, and neocarzinostatin, which all induce 3'-phosphoglycolate-terminated double strand breaks.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/DCLRE1C protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Endodeoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radicals,
http://linkedlifedata.com/resource/pubmed/chemical/Glycolates,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Zinostatin,
http://linkedlifedata.com/resource/pubmed/chemical/phosphoglycolate
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3547-58
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17121861-Bleomycin,
pubmed-meshheading:17121861-Cell Line,
pubmed-meshheading:17121861-DNA,
pubmed-meshheading:17121861-DNA Damage,
pubmed-meshheading:17121861-DNA Repair,
pubmed-meshheading:17121861-DNA-Activated Protein Kinase,
pubmed-meshheading:17121861-Endodeoxyribonucleases,
pubmed-meshheading:17121861-Free Radicals,
pubmed-meshheading:17121861-Glycolates,
pubmed-meshheading:17121861-Nuclear Proteins,
pubmed-meshheading:17121861-RNA Processing, Post-Transcriptional,
pubmed-meshheading:17121861-X-Rays,
pubmed-meshheading:17121861-Zinostatin
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pubmed:year |
2007
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pubmed:articleTitle |
Processing of 3'-phosphoglycolate-terminated DNA double strand breaks by Artemis nuclease.
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pubmed:affiliation |
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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